Melatonin

BACKGROUND

Melatonin is a natural hormone produced by the pineal gland, which is located near the center of the brain. The main function of melatonin is to regulate sleep cycles. The presence of light suppresses the production of melatonin, signaling to the body that it is time to wake up (1). Melatonin supplements can be natural or man-made, with the natural form coming from animal pineal glands. The supplement can be purchased over the counter and is not currently regulated by the United States Food and Drug Administration (USFDA) (2). Melatonin is typically used to treat sleep disturbances and correct irregular sleep cycles.

Melatonin was first discovered in 1958 by Aaron Lerner, a dermatology professor at Yale University. It was discovered when Lerner began research to determine the factor that caused the darkening of amphibian skin, and he was able to extract a small amount of the hormone from the pineal gland. The name melatonin came from the Greek word melas, which means black, or dark (3). Lerner and his colleagues originally tried to use melatonin supplementation to treat vitiligo and to reverse hyperpigmentation, which ultimately failed (4).

After Lerner’s initial discovery of melatonin, researchers elsewhere began observing the effects of melatonin on laboratory animals. It was soon discovered that melatonin can affect the brain and endocrine system (4). The first papers highlighting the neuroendocrine effects of melatonin were published in 1965 and explained how the hormone acts as a neurotransmitter in the central nervous system (3). Research on the pineal gland and melatonin kept expanding. In 1975, Lynch and colleagues proved that melatonin production follows a circadian rhythm and melatonin levels in the body are much higher at night (5). Nearly twenty-five years after Lerner’s discovery, indications of melatonin’s role in physiological, behavioral, and clinical conditions began to emerge (4).

The powerful antioxidant properties of melatonin were not discovered until 1993 by Poeggeler and colleagues, who proposed that melatonin could be used to prevent diseases that relate to aging (6). The first patent for melatonin as a sleeping aid was awarded to Richard Wartman in September of 1995 (7). Melatonin began getting much more attention in the 21st century as a method of treating various ailments due to its apparent lack of toxicity and side-effects (8).

TRADITIONAL USES

WHAT DOES SCIENCE TELL US?

Melatonin Probably Helps Support Sleep:

Melatonin is most commonly used to encourage sleep initiation, increase time spent asleep, and correct irregular sleep patterns (10).

Multiple studies have found melatonin to be highly beneficial in treating both elderly patients with insomnia (11,12) and children with insomnia (13). These studies reported no acute side-effects, long-term implications, withdrawal symptoms, or negative impacts on child development. Melatonin was also found to increase sleep time and was more effective than light treatment for children with insomnia (14). Similar results were seen in a study conducted among children and adolescents with autism spectrum disorder and insomnia. Melatonin increased sleep time and decreased sleep disturbances among this population (15). Furthermore, children with neurodevelopmental disorders who suffer from severe sleep problems may also benefit from melatonin supplementation, as sleep time was slightly increased over a three month period (16).

Melatonin has been found to be effective for improving sleep among individuals with different medical conditions as well. Melatonin may be useful for treating sleep disturbances among patients who have had a traumatic brain injury, while not having an effect on sleepiness during the daytime (17). Patients with both cancer and insomnia experienced quicker sleep onset and improved sleep quality with melatonin ingestion two hours before bedtime (18). Another study explored the effect of melatonin on sleep quality in patients who had just had surgery for breast cancer. This research concluded that sleep efficiency improved; although, subjective sleep quality measured using the visual analogue scale for sleep (VAS) and the Karolinska Sleeping Scale (KSS) did not improve (19). Melatonin was also found to be beneficial for patients undergoing coronary artery bypass graft surgery and was found to improve sleep more than Oxazepam, a common medication used to treat anxiety and insomnia (20).

Melatonin was found to be useful in reducing jet lag in those who are traveling across at least five time zones when the supplement was taken close to the bedtime of their destination (21). Furthermore, another study concluded that melatonin supplementation shortened the time it took to reinstate normal sleeping cycles and regain normal energy levels after jet lag from crossing twelve time zones (22). However, some studies found conflicting evidence regarding the effectiveness of melatonin for jet lag (23).

Melatonin treatment for shift work such as rotating schedules, night shifts, and extended hours can impact sleep schedules has shown variable results. Some research supports the use of melatonin as a treatment for shift work (24,25,26). Both sleep efficiency and sleep onset latency may improve for shift workers with difficulties falling asleep (27). One study found that melatonin produced a slight improvement for shift worker’s day sleep and alertness at night; although, this improvement was not found to be statistically significant (28).

Melatonin Possibly Improves Eye Health:

A 2006 study found that melatonin may improve eye health by protecting the retina and may slow the progression of macular degeneration (29). There is some evidence that melatonin is involved in the development of glaucoma, indicating that melatonin use may help with decreasing intraocular eye pressure (30). Reduced intraocular eye pressure is crucial for managing and preventing glaucoma, and melatonin has been shown to be effective at reducing this pressure in small amounts (31). This relationship, however, has not been extensively studied and more research is needed on the effects of melatonin on intraocular eye pressure and glaucoma.

Melatonin Might Help Support a Healthy Digestive Tract:

Due to the antioxidant properties associated with melatonin, this supplement has been found to protect against and help heal ulcers in the gastrointestinal tract (32,33). Irritable bowel syndrome symptoms such as stomach pain and bloating may be reduced with supplementation of melatonin (34,35). Another study concluded that melatonin may also help control gastrointestinal motility (36). Melatonin’s effect on gastrointestinal diseases has been extensively researched and is typically very effective for treating diseases related to the gastrointestinal tract.

Melatonin Possibly Helps Support Heart Health:

Melatonin possesses several protective characteristics that “may have utility in the treatment of several cardiovascular conditions”. It may be effective for lowering blood pressure and preventing heart tissue atrophy (37). Acute use of melatonin was found to have no effect on lowering blood pressure, but supplementation over longer periods of time lowered systolic and diastolic blood pressure with no changes to heart rate in both men and women (38,39). The impact of melatonin on coronary heart disease has not been well researched, although blood pressure in patients with coronary heart disease may be lowered with melatonin supplementation (40).

Melatonin Possibly Helps Support a Healthy Immune System:

Melatonin may play a useful role in protecting the immune system. One study concluded that melatonin has the possibility to improve the functioning of the immune system in elderly adults (41). Another study determined that melatonin may stimulate the immune system under normal or immunosuppressed conditions, which may help protect the body from things such as viruses and parasites. However, the same study noted that if the immune system has been under chronic stress, melatonin may have negative effects on the immune system (42). Furthermore, a decrease in melatonin production is associated with increasing age and has been proposed as a key contributor to immunosenescence and tumor growth (43). Due to melatonin’s stimulatory effect on the immune system, it has been suggested that melatonin prevents tumor formation and growth and may be helpful in preventing breast (44), uterine, and colorectal cancers (45,46). Melatonin’s antioxidant and immunostimulant properties may make it an oncostatic mediator (47). It is important to note that many of the human studies surrounding the effects of melatonin on cancer were in conjunction with normal cancer treatments, so the conclusions should be critically evaluated.

Melatonin Possibly Helps Support a Positive Mood:

Some evidence has pointed towards the use of melatonin to improve mood and to possibly help treat depression (48). Among a group of overweight postmenopausal women, melatonin, in combination with fluoxetine, was found to be associated with improved mood (49). However, these results cannot be attributed solely to melatonin. Furthermore, melatonin was discovered to decrease depressive symptoms in women with breast cancer (50), and most women stated an enhancement in mood and a decrease in depression after melatonin supplementation (51). However, a randomized clinical trial among postmenopausal women who had survived breast cancer noted no changes in depression; although, they did have improved sleep quality (52).

SAFETY

Interactions:

Major

Melatonin is known to causes tiredness, which may be dangerous when taken with other medications used for sedation.

Moderate

Taking melatonin supplements with birth control pills may result in an excess of melatonin in the body due to the fact that oral contraceptives seem to increase the amount of melatonin produced by the body (53).

There have been some reported cases of melatonin slowing blood clotting (54), which can make supplementation with anticoagulants such as aspirin, ibuprofen, warfarin, heparin, diclofenac, naproxen, enoxaparin, and dalteparin somewhat unsafe.

Verapamil can decrease the amount of melatonin the body releases (55), which would reduce the effectiveness of melatonin supplementation if these are taken in combination.

Minor

Consuming caffeine with melatonin supplements is not necessarily dangerous, although caffeine can lower melatonin levels (56). Consuming caffeine with melatonin supplements may reduce its effectiveness.

Side-Effects:

When taken orally, melatonin supplementation seems to be safe as it has many benefits with a small number of side effects (57).

See this National Center for Complementary and Integrative Health article on melatonin, this American Academy of Family Physicians article on melatonin, the Examine.com entry for melatonin, the Michigan Medicines Health Library entry for melatonin, or the WebMD entry for melatonin for more information.